Methods of optical spectroscopy and imaging are being developed for biomedical applications in non- or minimally invasive tissue diagnostics, including sensing molecular concentrations of delivered pharmaceutical or contrast agents, probing tissue physiologic status, and detecting early stages of disease in vivo. In tissue optics, one of the challenges is to obtain quantitative information despite the detected signal variability introduced by tissue morphology and optical absorption and scattering. The overall goal of this application is to develop, validate, and disseminate computational codes to numerically simulate photon migration characteristics useful for quantitative tissue spectroscopy and imaging. We will develop and employ innovative computational codes designed to model steady-state and time-resolved excitation and fluorescent light propagation in complex tissues approximately 102 -104 times faster than current methods. The computational resources developed here will be broadly applicable to problems in pre-clinical and clinical biomedical optical spectroscopy and imaging, including minimally-invasive applications requiring light delivery and collection via fiber-optic probe configurations. A multidisciplinary team of researchers with expertise in biomedical optics and clinical endoscopy has been assembled to ensure that these goals are achieved. The specific aims of this R01 grant proposal are: (1) To develop and numerically test novel computational codes for steady-state and time-resolved photon migration in tissues with complex morphologies and source-detector geometries; (2) To experimentally validate the computational codes developed in Aim #1; (3) To efficiently disseminate the computational codes developed in Aim #1 and validated in Aim #2 to the scientific community via download links and platform-independent user-interactive interfaces on the Pi's web-site. The innovative computational codes developed and validated here will be broadly applicable to a variety of problems in quantitative tissue optical spectroscopy and imaging. Rapid electronic dissemination via the internet will facilitate the generalized use of these digital tools, which will serve as a resource for a broad cross-section of researchers investigating problems in tissue optics. [unreadable] [unreadable] [unreadable]